This grant proposal has two major components. The first relates to the control of purine biosynthesis de novo. This aspect of the project is focused on amidophosphoribosyltransferase, the enzyme which catalyzes the first and rate-limiting reaction in this pathway. Studies are in progress to purify this enzyme, characterize its physical and kinetic properties, and determine what regulates its synthesis and degradation in the cell. The second component of this grant relates to the control of uric acid handling by the kidney. Studies are in progress to identify and characterize extra-renal factors which influence urate reabsorption and/or secretion by the nephron. These experiments utilize the animal model of the Dalmatian coach hound as a source of an extra-renal factor(s) which enhances urate clearance.